Phase II Trial of Aprepitant & Palonosetron for CINV Prevention w FOLFOX

OBJECTIVES:

Primary

• Evaluate the efficacy, in terms of nausea and vomiting control, of aprepitant, palonosetron hydrochloride, and dexamethasone, in preventing chemotherapy-induced nausea and vomiting in patients receiving FOLFOX or FOLFIRI chemotherapy for metastatic colorectal cancer.

Secondary

• Assess the percentage of patients with no emesis and no rescue therapy when treated with aprepitant, palonosetron hydrochloride, and dexamethasone during repeated courses of FOLFOX or FOLFIRI chemotherapy.
• Assess the effects of aprepitant on nausea, appetite, taste changes (via visual analogue scale), nutritional intake, and mucositis in these patients.
• Assess the safety of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Beginning 1 hour prior to the initiation of chemotherapy on day 1, patients receive oral aprepitant on days 1-3, oral dexamethasone on days 1-4, and palonosetron hydrochloride IV on day 1.

Nausea is assessed daily for up to 4 courses of chemotherapy.

Quality of life is assessed at baseline.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of colorectal cancer
• Metastatic disease
• Scheduled to receive 1 of the following chemotherapy regimens*:

• FOLFOX 4 (oxaliplatin, fluorouracil, leucovorin calcium)
• FOLFOX 6
• FOLFOX 7
• FOLFIRI (irinotecan hydrochloride, fluorouracil, leucovorin calcium) NOTE: *Regimens may also include cetuximab or bevacizumab
• No emesis and no requirement for antiemetic agents within 48 hours prior to beginning chemotherapy

• Single-agent benzodiazepines as a hypnotic allowed
• No chronic nausea

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy > 4 months
• White Blood Cell(WBC)count > 3,000/mm^³
• Absolute neutrophil count (ANC) > 1,500/mm^³
• Platelet count > 100,000/mm^³
• Bilirubin ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN if liver metastases present)
• Creatinine ≤ 1.5 times ULN
• Aspartate aminotransferase(AST) or Alanine aminotransferase (ALT) ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• Able to swallow tablets and capsules
• No known sensitivity to aprepitant, palonosetron hydrochloride, or dexamethasone
• Not pregnant or nursing
• Negative pregnancy test
• No history of consuming ≥ 5 alcoholic drinks/day within the past year
• No concurrent illness requiring systemic corticosteroids other than planned dexamethasone during study treatment
• No clinical signs of active systemic infection involving the gastrointestinal tract
• No active bowel obstruction

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy > Hesketh level 3

• Prior fluorouracil with or without leucovorin calcium or capecitabine allowed
• At least 30 days since prior investigational drugs
• At least 14 days since prior neurokinin-1 antagonists
• Concurrent hydrocortisone at physiologic replacement doses (≤ 30 mg/day) allowed
• No concurrent chronic antiemetic agents
• Concurrent hypnotics allowed
• Concurrent rescue antiemetics allowed